Process for preparation of terpene flavorants and novel intermediates therefor

ABSTRACT

A process for preparing compounds of the type of sinensal, which is suitable as a flavor-imparting agent of orange aroma, and novel intermediates including those having the general formula: WHEREIN R signifies a CH2OH, CHO or COOH group and the broken lines represent a double bond emanating from C-atom 4, are disclosed.

United States Patent [191 Bertele et al.

[ Mar. 18, 1975 PROCESS FOR PREPARATION OF TERPENE FLAVORANTS AND NOVEL INTERMEDIATES THEREFOR [75] Inventors: Erhard Bertele. Dubendorf; Peter Sehudel. Grut near Wetzikon. both [2!] Appl. No.: 742,178

[30] Foreign Application Priority Data July 7. I967 Switzerland 9749/67 Nov. 1, I967 Switzerland l539l/67 [52] US. Cl. 260/601 R, 260/339, 260/632 R.

[51] Int. Cl. C07c 47/20 58] Field of Search 260/60I, 601 R [56] References Cited UNITED STATES PATENTS 2.8 l9,3l2 H1958 ISlCI ct alt 260/601 FOREIGN PATENTS OR APPLICATIONS 813.539 5/l959 United Kingdom 260/60l X OTHER PUBLICATIONS Greiner. V. A., Journ. fur Prak. Ohemie, Vol. 13, 1961. pp. l58-l62.

Henne et al., Journ. of the Amer. Chem. Soc.. Vol. 65, pp. 2183-2I85, I943.

Finder. The Chemistry of the Terpenes, 1960, pp. 7. l6, and 28-31.

Sutherland. M.D.. Journ. of the Amer. Chem. Soc.. Vol. 74, page 2688, 1952.

Primary Examiner-Leon Zitver Assistant ExaminerR. H. Liles Attorney. Agent, or FirmThomas Cifelli. .Ir.

[5 7] ABSTRACT A process for preparing compounds of the type of sinensal, which is suitable as a flavor-imparting agent of orange aroma, and novel intermediates including those having the general formula:

wherein R signifies a CH Ol-l. CHO or COOH group and the broken lines represent a double bond emanating from C-atom 4. are disclosed 3 Claims. N0 Drawings PROCESS FOR PREPARATION OF TERPENE FLAVORANTS AND NOVEL INTERMEDIATES THEREFOR SUMMARY OF THE INVENTION This invention provides a commercially-feasible process for making unlimited quantities of compounds of the type of the previously-rare sinensal, thereby permitting the widespread use of this product as a flavorant to impart an orange flavor and aroma to food products such as orange drinks.

Novel intermediates, some of which also possess flavorant properties, are also the subject of this invention.

DETAILED DESCRIPTION OF THE INVENTION The process in accordance with this invention for the manufacture of compounds of formula I is characterized in that a compound of the formula is ozonized and the ozonization product which is obtained is decomposed to give a compound of general formula I.

Cis or trans ocimene or, preferably, myrcene can be used as the starting material of formula II.

If in formulae l and [I the double bond which is conjugated with the terminal double bond lies within the chain (as is the case in ocimene), formulae 1 and II are meant to represent not only the cis but also the trans isomers.

The ozonization of the trienes ll surprisingly proceeds with high selectivity, since the ozonide linkage is practically exclusively effected at the isolated double bond, and so the conjugated double bonds practically do not enter into reaction with the ozone.

The ozonization can be undertaken according to "methods known per se, by bringing ozone-containing gas into contact with the triene which is to be ozonized, conveniently by introduction of the gas into a preferably dilute solution of the triene. Presently preferred solvents are those which are inert to ozone, or at least display greater stability than the substance which is to be ozonized; for example, alkanes such as hexane, petroleum ether, cyclohexane; benzene and its derivatives; halogenated hydrocarbons such as carbon tetrachloride. chloroform, methylene chloride, methyl chloride, ethyl chloride, ethyl bromide; esters such as formic acid or acetic acid esters (ethyl acetate); ketones such as acetone or methyl ethyl ketone; ethers such as dimethyl ether, diethyl ether, tetrahydrofuran; acid anhydrides such as acetic anhydride; acid amides such as formamide, dimethylformamide; nitromethane etc. Among other solvents which may be used are those which enter into reaction with the ozonide which is primarily formed: for example, carboxylic acids (for example, formic acid, acetic acid, propionic acid); alcohols such as methanol, ethanol, propanol; water in admixture with acetone. Best suited are solvents which are able to hold the ozonization products in solution. Furthermore, low-boiling solvents are to be preferred. since these are usually readily separable from the reaction products. For the ozonization of myrcene and ocimene, particularly suitable solvents are, for example: methyl chloride, chloroform, carbon tetrachloride, benzene, acetone, ethyl acetate, methanol.

The concentration of the solution which is to be ozonized can vary within wide limits. In general, dilute solutions give better yields. On practical grounds, 5-20 percent solutions will usually be used.

Conveniently, not more than about 1 mol equivalent of ozone is allowed to act on the triene 11, in order to avoid an oxidation of the reaction products. Normally, an oxygen stream with an ozone content of about 2-10 percent is used. However, more dilute and more concentrated ozone mixtures also may be employed. If desired, oxygen-free ozone (as the gas or as a solution) may also be used.

The ozonization is advantageously carried out at temperatures below room temperature, conveniently at temperatures below 0C. Particularly good yields are obtained at temperatures within the range of about -50 to 90C.

The cleavage of the ozonization products which are primarily obtained to the compounds of general formula I can be undertaken according to methods which are known per se.

The alcohols of the formula may be obtained by treating the ozonization product which is formed with a powerful reducing agent, of the type known to be suitable to reduce ozonides to alcohols, such as a complex metal hydride (e.g. lithium aluminum hydride or sodium borohydride), hydrogen, catalytically activated by noble-or transition metals (e.g. palladium, platinum) or complexes of such metals (as for example tristriphenylphosphine-rhodiumchloride).

The aldehydes of the formula can be obtained from the ozonization products by treatment with a mild reducing agent (of the type known to be suitable to reduce ozonides to aldehydes); for example, an iodide (e.g. sodium or potassium iodide), sulphite, bisulphite (e.g. sodium bisulphite), with formaldehyde, sulphur dioxide, pyridine, hydrazine hy- 3 drate, a sulphide (e.g. dimethyl sulphide), hydroquinone, zinc or magnesium in acidic solution, Raneynickel, phosphorus (NU-compounds (e.g. phosphines such as triphenylphosphine, tri-loweralkyl-phosphites such as trimethylphosphite), hydrogen [catalytically activated by noble-or transitionmetals or complexes thereof (examples of such systems are Pt/l-l Pd/C/H2-)] The carboxylic acids of the formula (i.e. 4-methylene-5-hexenoic acid or 4-methyl-3,5- hexadienoic acid) may be obtained from the primary products of the ozonization by treatment with an oxidizing agent, for example, potassium permanganate, hydrogen peroxide, peracids, chromic acid, oxygen (catalyzed by manganese or silver salts), silver oxide, peracids (e.g. perbenzoic acid, peracetic acid), etc. Using aluminum hydrides (such as, for example, lithium aluminum hydride), the acids Ic can be reduced directly or, if desired, in the form of their esters, to the corresponding alcohols in a known manner. Likewise, the acids lc may be converted via the acid chlorides into the amides (e.g. the corresponding N-methyl anilides or N,N-dimethyl amides)which, as is known, can be transformed into the corresponding aldehydes of formula lb under the influence of aluminum hydrides (such as, for example, of diisobutyl aluminum hydride or lithium diethoxy aluminum hydride). The esters derived from the acids 10 may also be directly converted into the aldehydes of formula lb at lower temperatures.

The alcohols, aldehydes or carboxylic acids of formulae la, lb or 10 which are obtained by ozonization of the trienes ll and by subsequent reductive or oxidative cleavage of the ozonization products, as well as the triene acetals (lV-l and lV-2) and triene aldehydes (V-l and V-2) are new compounds which may be used as intermediate products for the manufacture of compounds with orange aroma, especially for the manufacture of the ,B-sinensal occurring in orange oil (Citrus sinensis) (trans B-sinensal: 2,6-dimethyllO-methylene- 2t,6t,ll-dodecatrienal), of isomers thereof (cis B-sinensal, cis and trans B-sinensal), as well as of analogues such as, for example, the corresponding alcohols or acid esters which are likewise distinguished by particular aromas (citrus fruit flavours), on the basis of which the compounds can be used for the aromatization, for example, of drinks,

B-sinensal and its isomers (VII), as well as the corresponding alcohol and acid ester analogues, X11 and XI, respectively, may be used to impart orange flavor in drinks by incorporation therein in very small amounts, e.g. from /2 to 5 parts per million. These flavorants may be used in conventional manner, for example, in the manner in which the known flavorant, aldehyde C-lO, is used.

The aldehyde lb-l obtainable from myrcene, or the corresponding alcohol la-l may be converted into cis and trans B-sinensal in accordance with the following schemes:

III

Scheme A Scheme B Myrcene (II-1) is converted into the aldehyde lb-l Myrcene (II-l) is converted by ozonisation and sub- (4-methylene-5-hexen-1-al) by ozonisation and subsesequent energetic reductive cleavage ofthe ozonisation quent mild reductive cleavage of the ozonisation prodproduct into the alcohol Ia-l (4-methylene-5-hexen-1- uct. The aldehyde thus obtained is reacted with a phos- 5 01). After transformation into the phosphorane VIII- 1 phorane of general formula III [wherein Ph represents this is reacted with the ketone acetal IX in a Wittig rea phenyl group and each R signifies a lower alkyl action to give the triene acetal IV-l which, as shown in group which can also be linked with each other to form scheme A, can then be worked up to give B-sinensal. By a lower alkylene group (e.g. ethylene)] in a Wittig reusing ocimene as startingmaterial the isomeric triene action to give a triene acetal of general formula IV-l. acetal IV-2 can be obtained similarly.

Formula IV-l includes the trans isomer IVa-l and the The transformation of the alcohol Ia-l into the phoscis isomer IVb-l. phorane VIII-l can, for example, be undertaken in such The manufacture of the phosphorane III (as also of a way that the alcoholic hydroxyl group is exchanged the phosphoranes additionally mentioned hereinafter) for an iodine atom and the 6-iodo-3-methylene-land the reaction with the carbonyl component Ib-l can hexene obtained is reacted with triphenyl-phosphine to be effected according to the methods of the Wittig regive the corresponding phosphonium iodide which, action which are known per se (see, for example, Anafter treatment with a strong base such as butyllithium, gewandte Chemie 71 (1959), 260). In doing so, one can then proceed to the reaction with the ketone acetal conveniently proceeds in such away that the carbonyl IX. component is added to a freshly prepared solution or Scheme C suspension of the phosphorane. The phosphorane VIII-l which is obtainable in accor- Thereupon, [if desired after separation of the mixdance with scheme B is reacted according to Wittig ture of the cis and trans isomers (e.g. by means of prewith the ketone ester of general formula X (wherein R parative gas h t hy the t i ne a etal IV-l signifies a-lower alkyl group) to give the tetraene ester or the isomer triene acetal IV-2 obtained from ocimene this ester 18 reduced to the Corresponding traene alcohol XII-l according to methods known per se .g. with lithium aluminium hydride), and the alcohol 2' Z'Z 7 2 f' 2 obtained is oxidised to the corresponding tetraene aldehyde VII-l (B-sinensal) according to methods known 7 '7 n per Se (e.g. with manganese dioxide). 1 Scheme D wherem R has the m meiamng as above 15 hydro" The triene aldehyde V-l obtained according to lysed cwespmdmg mm aldehyde of the Scheme A and B is reacted aCCOIdiHg to Wittig with the mula phosphorane XIII (wherein R is a lower alkyl group) 2 to give the tetraene ester XI-l and this is worked up aca 4 cording to Scheme C to give the tetraene aldehyde VII- V-f-J, In an analogous manner the isomeric triene aldehyde (including the trans isomer Va-l and the cis isomer- V-2 can be converted to the tetraene ester XI-2 one-cit Ch Y=CHCl-I 03 ccx =cu cu cu CH i'==CII-CHCH i=CI-I CH5- CI I=i-CH=CH XIII-2 R Q9 I I-l Vb-l) or to the triene aldehyde of formula and this worked up via the tetraene alcohol XII-2 J 3- CH t) CH CH C.. TCH C11 (DH-SI CH CH CH OH 2 h c t ci-i XII 2 oac-cti -Ci-Z- ==cu- 03- c --CH==CH to the tetraene aldehyde VII-2.

CH H The following Examples illustrate the invention, all

3 5 v? temperatures being given in degrees centigrade. The hydrolysis of the acetals IV-l and IV-2 to the aldehydes V-l and V-2 can be brought about according EXAMPLE I to the usual methods of acetal saponification. 73.5 mmol of ozone are introduced within approxi- Finally, the triene aldehyde V-l or V-2 is reacted, mately 3 hours into a solution, cooled to of 10 g again according to Wittig, to give the tetraene aldehyde (73.5 mmol) ofmyrcene in 50 ml ofmethanol. The still of the general formula VII-I or VII-2: 7 cold solution is then briefly flushed with nitrogen and OHC-FFCEk- CH CH aC== CH- CH CH VII -l (31-! CI-I CH OHC-C==CHCI-I -CH.,- C='-CH-CH,,-- CH=$-CI'I==CI-i VII-2 i CH CH 3 3 by reaction with a phosphorane VI. Formula VII-l intreated with 6.8 g mmol) of dimethyl sulphide. cludes the trans isomer VIIu-l (natural B-sinensal) and The cooling-bath is thereupon removed and the reacthe cis isomer VIlb-l. tion mixture allowed to warm up. After approximately EXAMPLE2 1.51 g (3.0 mmol) of finely powdered (4- ethylenedioxy-butyl)-triphenyl-phosphonium iodide are suspended in 10 ml of tetrahydrofuran and treated dropwise with a solution of 4.5 mmol of butyl-lithium in hexane. The solution turns red as the phosphonium iodide goes into solution as (4-ethylenedioxybutylidene)-triphenyl-phosphorane. After approximately minutes, 0.25 ml (4.5 mmol) of methyl iodide are added to this solution, which thereby becomes lighter, and the (4-ethylenedioxy-l-methylbutyl)- triphenyl-phosphonium iodide which is formed partially precipitates as an oil. After 10 minutes, 3.0 mmol of butyl-lithium in hexane are added dropwise and the 5 solution thereby again becomes dark red.

After 10 minutes there are added 330 mg (3.0 mmol) of 4-methylene-5-hexenal (lb-l) dissolved in 1 ml of tetrahydrofuran to the solution containing the phosphorane 111 (R+R =ethy1ene). The solution subsequently partially decolourises and after 30 minutes, 100 mg of sublimed potassium tertbutylate are added. The mixture is stirred for a further 1.5 hours, then taken up in pentane and the insoluble portion which;

separates out is decanted off. The pentane extract is subsequently washed with water until neutral and dried over sodium sulphate. After removal of the solvent, the residue is distilled. There are thus obtained 421 mg (63 percent) of a cis-trans isomer mixture of the triene acetal lV-l (R+R =ethylene) in the form of an oil with a boiling point l60/0.l mm; n =1.4930. lR-bands at 1600111, 1 145s, 900s cm.

The ratio of the trans isomer IVa-l (4-methyl-8- methylene-4t,9-decadienal ethylene acetal) to the cis isomer lVb-l (4-methyl-8-methylene-4c, 9-decadienal ethylene acetal) amounts to ca 1:1. The isomer mixture may be separated by means of gas-chromatography.

The (4-ethylenedioxy-butyl)-triphenyl-phosphonium iodide (melting point l72l77) used in this example can be obtained as follows: 4-chlorobutyric acid chlo' ride is reduced to 4-chlorobutanal according to Rosenmund, the aldehyde is acetalised with ethyleneglycol, the product obtained thereby is converted with sodium iodide into the ethylene acetal of 4-iodobutanal and the latter is reacted with triphenyl-phosphine.

EXAMPLE 3 146 mg (0.65 mmol) of the triene ethylene acetal of formula lV-l (cis-trans isomer mixture) are dissolved in 3.7 ml of dioxan and 1.2 ml of 0.1-N sulphuric aci The solution is boiled at reflux for 2 hours, the reaction product is taken up in ether, this solution washed until neutral with sodium bicarbonate solution and dried over sodium sulphate. After removal of the solvent, the oily residue is distilled. There are thus obtained 97 mg (83 percent) of a cis-trans isomer mixture of the triene aldehyde V- l ,4-methyl-8-methylene-4,9-decadienal, of

boiling point l0O/0.l mm.

In an analogous manner, the pure cis and trans isomers lVb-l and lVa-l (obtained from the isomer mixture lV-l by means of preparative gas chromatography) are saponified to the cis isomer Vb-l (4-methyl-8- methylene-4c, 9-decadienal) and to the trans isomer Va-l (4-methyl-8-methylene-4t,9-decadienal) respectively. n value and IR spectrum of the two isomers obtained are identical: n,, =l.4909; IR-bands at 2700111, 1725s, 1600m, 900s cm".

" EXAMPLE 4 175 mg (0.98 mmol) of the trans triene aldehyde Va-l (4-methyl-8-methylene-4t,9-decadienal) and 318 mg (1.0 mmol) of the phosphorane V1, (a-formylethylidene)-triphenyl-phosphorane, are dissolved in 5 ml of benzene. The solution is boiled at reflux for 40 hours, the benzene is thereupon removed by vacuum, the residue is treated with pentane, the phosphine oxide precipitates this way and is filtered off and the pentane is again evaporated from the filtrate. The residual oil is distilled. There are thus obtained 161 mg percent) of gas-chromatographically pure trans l3-sinensal VlIa-l (2,6-dimethyl-IO-methylene- 2t,6t,l l-dodecatrienal) of the approximate boiling point l00/0.1 mm; n =1.0577; IR-bands at 1700s, 1600w. 900s cm. i

In a corresponding manner, there are obtained by reaction of 158 mg (0.89 mmol) of the cis triene aldehyde Vb-1 with 290 mg-(0.9l mmol) of the phosphorane V1 157 mg (81 percent) of cis ,B-sinensal VIIb-l of the approximate boiling point 100/0.1 mm; n "=1.5078; IR-bands at 1700s, 1600w, 900s cm.

The phosphorane VI (melting point 220-222) can be obtained as follows: Ethyl iodide is reacted in benzene with triphenyl-phosphine to give ethyl-triphenylphosphonium iodide, and this is brought to reaction with butyl-lithium and formic acid methyl ester.

EXAMPLE 5 cooled to in the course of about 4 hours. The solution is then briefly flushed with nitrogen, in order to expel excess ozone. A solution of 2.1 g (55.5 mmol) of sodium borohydride in ml ofmethanol/water 1:1) is thereupon rapidly added dropwise at 0 and the mixture is then allowed to react at room temperature for l-2 hours. The solution is thereupon concentrated to one-third of the volume at the rotary evaporator (bath temperature 4050), the residue taken up in ether, the ether solution thoroughly shaken twice with 1- molar acetic acid, washed neutral, dried over sodium sulphate and the ether evaporated off. After fractional distillation, there are obtained 5.8 g (48 percent) of gas-chromatographically pure 4-methylene-5-hexenl 01 of boiling point 73-75/ll mm; n,, =l.4790; 1R- bands at 3350s, l605m, 900s cm".

EXAMPLE 6 10 g (89 mmol) of 4-methylene-5-hexene- 1 -01 and 22 g (116 mmol) of tosyl chloride are dissolved in 50 ml extracts are again thoroughly shaken once each with l-N hydrochloric acid and with l-N soda solution. After having been washed neutral with water, the ether solution is dried over sodium sulphate. After evaporation of the ether (bath-temperature 40-50, ca. 300 mg Hg), there remain approximately 12 g of a crude mixture of the corresponding diene tosylate and diene chloride (6-chloro-3-methylene-l-hexene). The chloride may be purified by distillation (boiling point 46/l mm; n =l.477l but the tosylate is thereby decomposed. For this reason, the tosylate-chloride mixture is converted as such into the iodide.

The tosylate-chloride mixture is dissolved in a suspension of 250 ml of acetone and 80 g (534 mmol) of sodium iodide and boiled at reflux temperature with stirring for 16 hours. Ca 200 ml of acetone are thereafter distilled off. The residue is taken up in water/ether. The ether extracts are thoroughly shaken, once with sodium thiosulphate solution and once with water. After having been dried over sodium sulphate, the ether is evaporated off. Fractional distillation yields 2 fractions:

1. Boiling point 50"68/l l rnm: 4.1 g; n l.4786

(mainly chloride) 2. Boiling point 6876/1l mm; 4.0 g; n *=1.532l

(iodide with trace of chloride) 6 g (27 mmol) of 6-iodo-3-methylene-l-hexene and 14 g (53 mmol) of triphenyl-phosphine are dissolved in 10 ml of benzene. The mixture is allowed to react at 60 for 24 hours. The (4-methylene-5-hexenyl)-triphenylphosphonium iodide which crystallizes out after this time is filtered off by suction, washed with benzene and dried. Yield 10.9 g (84 percent); melting point 146.

The 6-lodo-3-methylene-l-hexene can also be obtained from 4-methylene-5-hexene-l-ol as follows:

2.02 g (4.5 mmol) of methyl-triphenyloxyphosphonium iodide are dissolved in 3 ml ofabsolute methylene chloride and treated at with 0.5 g (4.5 mmol) 4-methylene-5-hexen-l-ol (dissolved in 0.6 ml of methylene' chloride). After minutes, the mixture is heated and then boiled at reflux temperature for 3 hours. There are thus obtained 333 mg of gaschromatographically pure 6-iodo-3-methylene-1- hexene with n =1.5478; lR-bands at 1600m, 9005 cm.

EXAMPLE 7 11.4 g (2.3 mmol) of (4methylene-5-hexenyl)-triphenylphosphonium iodide are suspended in 80 ml of absolute tetrahydrofuran and m1 of absolute ether. 19.4 ml of 1.2-N butyl-lithium solution mmol of butyl-lithium) in hexane are added to the suspension at 20. The solution thereby turns red. After minutes the solution is cooled to 60 and treated with 4.5 g (2.6 mmol) of 4-oxo-pentanal diethyl acetal (IX: R=C H whereby the red solution decolourises. The mixture is subsequently stirred at room temperature for a further 3.5 hours, then poured onto ice-water and extracted with hexane. After drying over sodium sulphate, the hexane is evaporated off. The residual oil is chromatographed on the 10-fold amount of aluminium oxide. Through elution with benzene, there are obtained 2.6 g of thin layer chromatographically uniform material and therefrom, after distillation, 2.4 g (40 percent) of an oil of boiling point 90/0.1 mm. On the basis of a gas-chromatographic analysis, this product is a Cis/trans isomer mixture (2:1) of the triene acetal lV-l (R=C H lR-bands at 1600m. 900s cm".

12 EXAMPLE 8 2.0 g (8.0 mmol) of Cis/trans trieneacetal lV-l (R=C H are dissolved in 25 ml of dioxan and 8 ml of 0.1-N sulphuric acid. The solution is allowed to stand at room temperature for 3 hours. It is neutralised by addition of solid sodium bicarbonate and the product is extracted with ether. After drying the ether extract over sodium sulphate, evaporation of the solvent and distillation of the residue, there are obtained 1.1 g (77 percent) of cis/trans triene aldehyde V-l of boiling point l00/0.1 mm; n -1.4831; lR-bands at 1730s, 1600m, 900s cm.

EXAMPLE 9 4 g (8.3 mmol) of finely powdered and well dried (4- methylene-S-hexenyl)-triphenyl-phosphonium iodide are suspended in 24 ml of absolute tetrahydrofuran and 8 ml of absolute ether and treated at 20 with 6.8 ml of 1.2-M (8.2 mmol) butyl-lithium solution in hexane, whereby the characteristic red colouration rapidly appears. After having reacted for 30 minutes at -20, the solution is cooled to and then treated with 1.52 g (8.3 mmol) of 6-oxo-2-methyl-2-heptenoic acid ethyl ester X-l (R =C H Very rapid decolourisation of the solution is thereby effected. The mixture is allowed to reach room temperature and stirred for a further 2.5 hours, then poured onto ice/water and extracted with ether. After drying over sodium sulphate, the solvent is evaporated off. There remain 3.7 g of a crude oil which, for the purpose of purification, is subjected to chromatography on the four-fold amount of silica gel (Merck 0.2-0.5). 1.3 g of the ester XI (thin layerchromatographically pure)(R =C l-l namely 2,6- dimethyll0-methylene-2,6,l l-dodecatrienoic acid ethyl ester, are eluted with benzene. By a distillation of this product there are obtained 895 mg (41 percent) of this ester with n,, =1.4938. On the basis of gaschromatographic analysis, this is an approximately 1:1

mixture of the 6-cis and the 6-trans isomers (2,6-'

dimethyl-l0-methylene-2t,6c, ll-dodecatrienoic acid ethyl ester and 2,6-dimethyl-l0-methylene-2t,6t,l ldodecatrienoic acid ethyl ester).

lR-bands at 1705s, 1650w, l600w, 900s cm.

The cis/trans isomer mixture can be separated gasch'romatographically. Cis isomer: n =l.4942; trans isomer: n --l.4946.

EXAMPLE 10 33 mg (0.25 mmol) anhydrous aluminium chloride and 31 mg (0.78 mmol) of lithium aluminium hydride are suspended in 1 ml of absolute ether. To this suspension there are added at 80, with the exclusion of moisture, mg (0.34 mmol) ofthe cis/trans ester Xl-l obtained in accordance with Example 9 in a little ether. The reaction mixture is stirred at -30 for 15 minutes, subsequently again cooled to 80 and then treated with about 0.5 ml of methanol. The mixture is poured onto ice/0.1-N hydrochloric acid and extracted with ether. The ether solution is washed neutral with water and dried over sodium sulphate. The oil remaining after evaporation of the ether is distilled. There are thus obtained 58 mg (76 percent) of the colourless, gaschromatographically pure cis/trans alcohol XII-l (2,6- dimethyl-l-methylene-2t,6c/t,ll-dodecatrienol). IR- bands at 3300s, l600m, 900s cm". Boiling point approximately l00/0.l mm.

EXAMPLE ll 40 mg (0.18 mmol) of the cis/trans alcohol XII-l obtained in accordance with Example are added to a suspension of 140 mg of manganese dioxide in 1 ml of hexane. The mixture is stirred in a nitrogen atmosphere at room temperature for 21 hours, subsequently filtered and the filtrate freed from hexane. By distillation of the residue, there are obtained 19 mg (48 percent) of colourless, gas-chromatographically pure cis/trans aldehyde VII-l (2,6-dimethyl-l0-methylene-2t,6c/t,1 ldodecatrienal) of boiling point approximately l00/0.l mm; IR-bands at 1695s, 1650m, 1600m, 900s cm.

"Wampum methyl-8-methylene-4t,9-decadienal) are added to a suspension, previously cooled to -20, of 3.3 g (9.1 mmol) of (a-carbethoxyethylidene)-triphenyl phosphorane in 12 ml of absolute methylene chloride, whereupon the reaction mixture is allowed to stand for 30 hours at 20. After removal of the solvent through vacuum, hexane is added, the precipitated phosphine oxide is filtered off and the filtrate is concentrated. The residue is distilled in a bulb tube. There are thus obtained 1.25 g (77 percent) of tetraene ester XI-l (2.6-dimethyl-10-methyIen-2t,6t, ll-dodecatrienoic acid ethyl ester) in the form of a colourles oil of b.p. l00/0,l mm; IR-bands at 1720s, l650w, L600w, 900s cm. M r

37 mmol of ozone are passed in the course of 80 minutes through a solution, previously cooled to -80, of 5 g (37 mmol) of ocimene in 50 ml of methanol. The reaction mixture is thereafter briefly flushed with nitrogen. A solution of 700 mg (19 mmol) of sodium borohydride in 20 ml ofmethanol/water is then added drop wise at 0. The mixture is allowed to react at room temperature for 2 hours. The mixture is then concentrated to ca one-third of the volume at the rotary evaporator (bath 3540/20 mm Hg). The residue is taken up in ether, throughly shaken with l-N acetic acid and then again washed neutral with sodium bicarbonate solution. After drying the organic phase over sodium sulphate and evaporation of the ether, there remain 3.7 g of crude material which, after fractional distillation, yield 1.4 g (34 percent) of 4-methyl-3,5-hexadien-l-ol of boiling point 808 l/ll mm,n =l.4931.IR-bands at 3300s, l650w, l6l0w, 900s cm".

The cis/trans isomer mixture of 4-methyl-3,5-hexadien-l-ol may be resolved, e.g. by means of gas chromatography, into the pure cis and the pure trans isomer.

EXAMPLE 14 2.4 g (5.36 mmol) of triphenylphosphite-methoiodide are dissolved in 4.5 ml of methylene chloride and treated with 300 mg (2.68 mmol) of 4-methyl-3,5-hexadien-l-ol (cis/trans isomere mix ture). The reaction mixture is refluxed for 15 minutes in a nitrogen atmosphere. It is subsequently diluted with ether, the ether layer washed three times with ice- 3 cold 0.1 N soda lye then twice with water and then dried over sodium sulfate. After removal of the solvent by vacuum an oil remains, which is purified by chromatography on 10 g ofSilicagel (Merck 0.5-0.02). After elution ofthe column with hexane, there are obtained 480 mg (60 percent) of pure 6-iodo-3-methyl-l,3- hexadiene of b.p. /ll mm; n -1.5656; IR-bands at 1650m, 1610m, 900s cm".

In an analogous manner, the pure cis and trans iodide can be obtained starting from the corresponding pure cis ortrans isomer respectively.

The 6-iodo-3-methyl-l ,3-hexadiene obtained is converted in analogy to the method described in Example 6 with triphenyl phosphine to the (4-methyl-3,5- hexadienyD-triphenyl phosphonium iodide. Thereby the phosphonium salt of a) the cis/trans isomer mixture of m.p. ll3120; b) the trans isomer of m.p. l26l35; c) the cis isomer of m.p. 102-1l0, are obtained with a yield of about 90 percent.

i "EXAMPLE 15 The phosphonium iodide obtained (4-methyl-3,5- hexadienyl)-triphenyl-phosphonium iodide) is condensed in a Whittig reaction with 4-oxo-pentanal diethyl acetal (IX:R =C H to the corresponding triene acetal (4,8-dimethyl-4,7,9-decatrienal diethylacetal). The reaction is carried out in an analogous manner to the Wittig reaction described in Example 7. Starting from pure cis and from pure trans phosphonium iodide, there is obtained, respectively, an approximately 7:3 mixture of A -cis/trans,A -cis and of A cis/trans, A- trans triene acetal. B.p. in the bulb t-ube about /0.1 mm; IR -bands at 1650m, l600m, 895s cm. The isomers may be resolved by gas chromatography.

EXAMPLE 16 The obtained triene acetal is saponified to the corresponding triene aldehyde (4,8-dimethyl-4,7,9-

decatrienal) in analogy to the process of Example 8. B.p. in the bulb tube about 90/O.l mm; IR-bands at 270m, 1740s, 1650m, 1600m, 900m cm.

EXAMPLE 17 EXAMPLE 18 By reduction of the obtained all trans tetraene ester (2,6,I0-trimethyl-2t, 6t, 9t, ll-dodecatetraenoic acid ethyl ester) in analogy to the process described in Example 10, there is obtained the corresponding all-trans tetraene alcohol (2,6,10-trimethyl-2t, 6t, 9t, 11- dodecatetraenol). B.p. in the bulb tube about 100-110/O,1 mm; IR-bands at 3350s, 1650111, l6l0m, 995m, 895m cm' EXAMPLE 19 By oxidation of the obtained all-trans tetraene alcohol (2,6,l0-trimethyl-2t, 6t, 9t, ll-dodecatrienol) in analogy to the process described in Example 1 1, there is obtained the corresponding all-trans tetraene alde- EXAMPLE 20 1,6 g of 4-methylene-5-hexene-l-al (see Example 1) are dissolved, together with 5,5 g of silver nitrate, in 14 ml of ethyl alcohol and 7 ml of water. 49 ml of in sodium hydroxide are added to the solution and the mixture is shaken for 20 hours at room temperature. The silver and the silver oxide are filtered off and the filtrate is extracted with pentane. 240 mg of the starting aldehyde are recovered. The aqueous phase is acidified with hydrochloric acid and extracted thrice with ether. The ether-extract is washed until neutral, dried and the solvent evaporated. Through a subsequent distillation in a bulb tube there are obtained 900 mg of a colorless oil; (50 percent of the theory); b.p. (bulb tube) of the 4-methylene-5-hexaenoic acid 90/O,1 mm, n l,4752. lR-bands at 1715s, l600m, 910m.

Esterification of this product with diazomethane yields the corresponding methylester; b.p. (bulb tube) 85/ll mm, n 1,4605. IR bands at 3000s, 1740s, l640w, 1600m, 1440s, 900s.

The foregoing illustrates the practice of this invention, which, however, is not to be limited thereby but is to be construed as broadly as permissible in view of the prior art and limited solely by the appended claims.

What is claimed is:

1. The process which comprises ozonizing a solution of a product having the formula:

at temperatures below ambient room temperature with not more than an equimolecular equivalent of ozone decomposing the resulting ozonized product, in the presence of a reducing agent suitable for reducing ozonization products to aldehydes, selected from the group consisting of an iodide, a sulphite, a bisulphite, formaldehyde, sulphur dioxide, pyridine, hydrazine hydrate, a sulphide, hydroquinone, zinc or magnesium in acidic solution, Raney-nickel, phosphorus (Ill)- compounds, tri-lower alkyl-phosphites and hydrogen, to form the product having the formula:

reacting said aldehyde with a phosphorane of the general formula:

CH CH wherein R has the same meaning as above, hydrolyzing, the triene acetal which is obtained to the triene aldehyde of the formula:

and reacting this triene aldehyde with a phosphorane of the general formula:

OHC-Cf =P (Ph) 3 9 wherein Ph has the above significance, to give the corresponding tetraene aldehydeoftheformula:

CH 3 CH CH 2. The process of claim 1, wherein the trans isomer of the triene acetal mixture is isolated therefrom prior to hydrolysis and reaction with the phosphorane so as to yield trans-B-sinensa].

3. The process of claim 1, wherein the cis-isomer of the triene acetal mixture is isolated therefrom prior to hydrolysis and reaction with the phosphorane so as to 

1. THE PROCESS WHICH COMPRISES OZONIZING A SOLUTION OF A PRODUCT HAVING THE FORMULA:
 2. The process of claim 1, wherein the trans isomer of the triene acetal mixture is isolated therefrom prior to hydrolysis and reaction with the phosphorane so as to yield trans- Beta -sinensal.
 3. The process of claim 1, wherein the cis-isomer of the triene acetal mixture is isolated therefrom prior to hydrolysis and reaction with the phosphorane so as to yield cis Beta -sinensal. 